Formulation optimization and in vitro antibacterial ability investigation of azithromycin loaded FDKP microspheres dry powder inhalation

Azithromycin loaded fumaryl diketopiperazine(FDKP) dry powder inhalation was designed and prepared for the treatment of community-acquired pneumonia.The solubility of FDKP and stability of azithromycin solution was investigated.Formulation of azithromycin loaded FDKP microparticle was investigated and optimized by the single factor experiment.High-pressure homogenization and spray drying conditions were also optimized to prepare the particles by spray drying azithromycin dissolved FDKP microparticle suspension at pH 4.5.The in vitro antibacterial efficiency and in vitro dispersion performance was also investigated to confirm the antibacterial efficiency,dispersion and deposition behavers.FDKP/azithromycin mass ratio(3:2) was the optimized formulation of azithromycin loaded FDKP microparticle with the maximal drug loading efficiency.High-pressure homogenization and spray drying conditions were also optimized.The in vitro antibacterial results indicated that only with the antibiotic concentration higher than mutant prevention concentration could totally inhibit the reproduction of bacteria.In vitro dispersion performance of azithromycin loaded FDKP microparticles(AZM@FDKP-MPs) also shows remarkable improvement of dispersion and deposition behavers of AZM.AZM@FDKP-MPs dry powder inhalation as a targeting delivery route has better potential for lung infection treatment.